Clinical Pharmacology, Takeda Development Center Americas, One Takeda Parkway, Deerfield, IL, 60015, USA,
Clin Drug Investig. 2013 Oct;33(10):727-36. doi: 10.1007/s40261-013-0117-6.
The identification and quantification of potential drug-drug interactions is important for avoiding or minimizing the interaction-induced adverse events associated with specific drug combinations. Clinical studies in healthy subjects were performed to evaluate potential pharmacokinetic interactions between vortioxetine (Lu AA21004) and co-administered agents, including fluconazole (cytochrome P450 [CYP] 2C9, CYP2C19 and CYP3A inhibitor), ketoconazole (CYP3A and P-glycoprotein inhibitor), rifampicin (CYP inducer), bupropion (CYP2D6 inhibitor and CYP2B6 substrate), ethinyl estradiol/levonorgestrel (CYP3A substrates) and omeprazole (CYP2C19 substrate and inhibitor).
The ratio of central values of the test treatment to the reference treatment for relevant parameters (e.g., area under the plasma concentration-time curve [AUC] and maximum plasma concentration [C max]) was used to assess pharmacokinetic interactions.
Co-administration of vortioxetine had no effect on the AUC or C max of ethinyl estradiol/levonorgestrel or 5'-hydroxyomeprazole, or the AUC of bupropion; the 90 % confidence intervals for these ratios of central values were within 80-125 %. Steady-state AUC and C max of vortioxetine increased when co-administered with bupropion (128 and 114 %, respectively), fluconazole (46 and 15 %, respectively) and ketoconazole (30 and 26 %, respectively), and decreased by 72 and 51 %, respectively, when vortioxetine was co-administered with rifampicin. Concomitant therapy was generally well tolerated; most adverse events were mild or moderate in intensity.
Dosage adjustment may be required when vortioxetine is co-administered with bupropion or rifampicin.
识别和量化潜在的药物-药物相互作用对于避免或最小化特定药物组合相关的相互作用诱导的不良事件非常重要。在健康受试者中进行了临床研究，以评估文拉法辛（Lu AA21004）与合用药物之间的潜在药代动力学相互作用，包括氟康唑（细胞色素 P450 [CYP] 2C9、CYP2C19 和 CYP3A 抑制剂）、酮康唑（CYP3A 和 P-糖蛋白抑制剂）、利福平（CYP 诱导剂）、安非他酮（CYP2D6 抑制剂和 CYP2B6 底物）、炔雌醇/左炔诺孕酮（CYP3A 底物）和奥美拉唑（CYP2C19 底物和抑制剂）。
使用相关参数（例如，血浆浓度-时间曲线下面积 [AUC] 和最大血浆浓度 [C max]）的测试治疗与参考治疗的中心值比值来评估药代动力学相互作用。
文拉法辛合用对炔雌醇/左炔诺孕酮或 5'-羟基奥美拉唑的 AUC 或 C max 或安非他酮的 AUC 没有影响；这些中心值比值的 90%置信区间在 80-125%范围内。文拉法辛与安非他酮（分别增加 128%和 114%）、氟康唑（分别增加 46%和 15%）和酮康唑（分别增加 30%和 26%）合用使文拉法辛的稳态 AUC 和 C max 增加，而与利福平合用使文拉法辛的 AUC 和 C max 分别减少 72%和 51%。同时治疗通常耐受良好；大多数不良事件的强度为轻度或中度。
当文拉法辛与安非他酮或利福平合用时可能需要调整剂量。
